studies

1212A AASLD ABSTRACTS HEPATOLOGY, October, 2015
equal to that of Pegasys 180μg. Results: 32 subjects entered
the trial and 31 subjects completed study treatment. Groups
were well generally matched (65% male, 12.5% HBeAg-negative,
mean HBV DNA approximately 7.0 log10 IU/mL) at
each group with HBV genotypes reflective of the population.
rHSA/IFNα2a and Pegasys have shown antiviral activity and
acceptable safety, tolerability. rHSA/IFNα2a was better tolerated
than Pegasys such as neutrophil absolute value, white
blood cell count, platelet count, hemoglobin and albumin
decreased more at Pegasys group. Mean changes in serum
HBV DNA were -1.32-2.13-1.10-2.48 log10 IU/mL for 600,
750, and 900μg groups and Pegasys group after treatment.
E antigen quantitation decreased more and normalization rate
of ALT and AST were higher at rHSA/IFNα2a group. Half-life
(t1/2) of rHSA/IFNα2a is 120 to 140 hours and duration of
antiviral activity that indicate potential suitability for dosing
intervals of 2 weeks or longer. Serum IFNα2a area under the
curve and maximum concentration increased with dose escalating.
IFNα2a Accumulation is not obvious at each group.
Pharmacokinetics of the last dose except t1/2 and Kinetics of
viral decline were similar between rHSA/IFNα2a 750μg and
Pegasys. Conclusions: rHSA/IFNα2a was safe and well tolerated;
declines in HBV DNA were similar to Pegasys evaluated.
rHSA/IFNα2a 750μg has been selected for further hepatitis B
clinical development.
Disclosures:
The following authors have nothing to disclose: Hong Zhang, Min Wu, Qingmei
Li, xiaojiao li, Yanhua Ding, Junqi Niu
2059
Association between ALT flares and HBeAg loss and
HBsAg decline in Patients with Chronic Hepatitis B
during treatment with Tenofovir Disoproxil Fumarate or
Adefovir Dipivoxil
Patrick Marcellin 1 , Edward J. Gane 2 , Zahary Krastev 3 , Selim
Gurel 4 , Geoffrey M. Dusheiko 5 , Anuj Gaggar 6 , Benedetta Massetto
6 , Kyungpil Kim 6 , John F. Flaherty 6 , Mani Subramanian 6 ,
Harry L. Janssen 7 , Maria Buti 8 ; 1 Hôpital Beaujon, Clichy, France;
2 Auckland City Hospital, Auckland, New Zealand; 3 University
Hospital St. Ivan Rilsky, Sofia, Bulgaria; 4 Uludag Universitesi Tip
Fakultesi, Bursa, Turkey; 5 Royal Free Hospital, London, United
Kingdom; 6 Gilead Sciences, Inc., Foster City, CA; 7 University of
Toronto, Toronto, ON, Canada; 8 Universitari Vall d’Hebron and
Ciberehd, Barcelona, Spain
Background and Aims: Increase in ALT levels (flares) are
observed after the initiation of oral antiviral therapy and
thought to be immune-mediated. We evaluated the association
between ALT flares during the first 48 weeks of treatment with
tenofovir disoproxil fumarate (TDF) or adefovir dipivoxil (ADV)
and HBeAg loss and HBsAg decline. Methods: HBsAg levels
were determined by Abbott Assay (linear range 0.05-250
IU/mL; quantification test on undiluted samples, and at dilutions
of 1:500 and 1:999) in 245 and 359 chronic infected
HBeAg-positive and HBeAg-negative patients, respectively. ALT
flare was defined as ALT >2x baseline and >5x upper limit
of normal during the first 48 weeks of treatment. HBeAg loss
and HBsAg decline were evaluated 24 weeks after a flare.
Logistic regression analyses were performed to examine host
and viral baseline factors (including viral load, HBV genotype,
HBeAg status and HBsAg level) associated with flares. Significant
factors in univariate analyses were examined in a multivariate
model. Results: 23 HBeAg-positive patients (9%) and 5
HBeAg-negative patients (1%) experienced ALT flares during
the first 48 weeks of treatment. All ALT flares were considered
not clinically significant except for one which was reported as
a transient mild adverse event. Among HBeAg-positive patients,
HBeAg loss and HBsAg decline were greater in patients who
had ALT flares (Table, p